Tadanobu Irie

Electrical Storm in Patients with Brugada Syndrome is Associated with Early Repolarization

Background—Electrical storms (ESs) in patients with Brugada syndrome (BrS) are rare though potentially lethal. Methods and Results—We studied 22 men with BrS and ES, defined as ≥3 episodes/d of ventricular fibrillation (VF) and compared their characteristics with those of 110 age-matched, control men with BrS without ES. BrS was diagnosed by a spontaneous or drug-induced type 1 pattern on the ECG in the absence of structural heart disease. Early repolarization (ER) was diagnosed by J waves, ie, >0.1 mV notches or slurs of the terminal portion of the QRS complex. The BrS ECG pattern was provoked with pilsicainide. A spontaneous type I ECG pattern, J waves, and horizontal/descending ST elevation were found, respectively, in 77%, 36%, and 88% of patients with ES, versus 28% (P<0.0001), 9% (P=0.003), and 60% (P=0.06) of controls. The J-wave amplitude was significantly higher in patients with than without ES (P=0.03). VF occurred during undisturbed sinus rhythm in 14 of 19 patients (74%), and ES were controlled by isoproterenol administration. All patients with ES received an implantable cardioverter defibrillator and over a 6.0±5.4 years follow-up, the prognosis of patients with ES was significantly worse than that of patients without ES. Bepridil was effective in preventing VF in 6 patients. Conclusions—A high prevalence of ER was found in a subgroup of patients with BrS associated with ES. ES appeared to be suppressed by isoproterenol or quinidine, whereas bepridil and quinidine were effective in the long-term prevention of VF in the highest-risk patients.

The prevalence of early repolarization in Wolff-Parkinson-White syndrome with a special reference to J waves and the effects of catheter ablation

We determined the prevalence of J waves in the electrocardiograms (ECG) of 120 patients with Wolff-Parkinson-White syndrome in comparison with J-wave prevalence in a control group of 1936 men and women with comparable demographic and ECG characteristics and with normal atrioventricular conduction. J waves were present only during manifest preexcitation in 22 of 120 patients (18.3%), disappearing after catheter ablation and suggesting that J waves were associated with the presence of preexcitation. J waves were present in 19 (15.8%) of 120 patients only after ablation, apparently having been masked by early depolarization of the preexcited myocardial region, and in 22 patients (18.3%), J waves were not altered significantly by preexcitation. Thus, the overall J-wave prevalence was 52.5% (63/120) and, excluding those apparently due to preexcitation, 34.8% (41/120), both substantially higher than the prevalence (11.5%) in the control group (P < .001 for both). The patients with J waves appearing only during preexcitation were younger, predominantly females. The presence of J waves after ablation was associated with a history of atrial fibrillation and shorter ventricular effective refractory period. It is concluded that the prevalence of J waves is high in patients with Wolff-Parkinson-White syndrome and is influenced by manifest preexcitation.

Atypical Fast-Slow Atrioventricular Nodal Reentrant Tachycardia Incorporating a "Superior" Slow Pathway: A Distinct Supraventricular Tachyarrhythmia

Background— The existence of an atypical fast-slow (F/S) atrioventricular nodal reentrant tachycardia (AVNRT) including a superior (sup) pathway with slow conductive properties and an atrial exit near the His bundle has not been confirmed. Methods and Results— We studied 6 women and 2 men (age, 74±7 years) with sup-F/S-AVNRT who underwent successful radiofrequency ablation near the His bundle. Programmed ventricular stimulation induced retrograde conduction over a superior SP with an earliest atrial activation near the His bundle, a mean shortest spike-atrial interval of 378±119 milliseconds, and decremental properties in all patients. sup-F/S-AVNRT was characterized by a long-RP interval; a retrograde atrial activation sequence during tachycardia identical to that over a sup-SP during ventricular pacing; ventriculoatrial dissociation during ventricular overdrive pacing of the tachycardia in 5 patients or atrioventricular block occurring during tachycardia in 3 patients, excluding atrioventricular reentrant tachycardia; termination of the tachycardia by ATP; and a V-A-V activation sequence immediately after ventricular induction or entrainment of the tachycardia, including dual atrial responses in 2 patients. Elimination or modification of retrograde conduction over the sup-SP by ablation near the right perinodal region or from the noncoronary cusp of Valsalva eliminated and confirmed the diagnosis of AVNRT in 4 patients each. Conclusions— sup-F/S-AVNRT is a distinct supraventricular tachycardia, incorporating an SP located above the Koch triangle as the retrograde limb, that can be eliminated by radiofrequency ablation.

A novel KCNQ1 splicing mutation in patients with forme fruste LQT1 aggravated by hypokalemia

BACKGROUND Several KCNQ1 splicing mutations have been identified in patients with type-1 long QT syndrome (LQT1). It was suggested that the clinical severity may differ according to the aberrant splicing products. There may be precipitating factors that cause cardiac events in those with a mild clinical phenotype (forme fruste LQT1). METHODS AND RESULTS We analyzed the KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes in 31 consecutive LQTS patients. A novel KCNQ1 1251+1G>A (IVS9+1G>A) mutation was identified in three probands and their two relatives. The QT interval in all of the five individuals with mutation was not much prolonged in the absence of precipitating factors (mean QTc was 461±30ms.). Two of the five individuals with mutation were symptomatic. One patient (a 38-year-old female) had experienced recurrent episodes of syncope due to ventricular tachyarrhythmias (VTAs) accompanied by QT prolongation (QTc: 750ms) when the serum potassium concentration ([K(+)]) was 2.7mEq/L. After correction of [K(+)], the QTc interval was shortened to 515ms, and the occurrence of VTAs ceased. Another patient (a 22-year-old female) was resuscitated from cardio-pulmonary arrest due to VTAs. Just after resuscitation, the QTc interval was 629ms, and [K(+)] was 2.9mEq/L. After correction of [K(+)], the QTc interval was dramatically shortened to 440ms. In order to identify abnormal splicing products of the responsible mutation, we analyzed the reverse transcription-polymerase chain reaction products from peripheral bloods of the mutation carrier, and identified exon 9-skipping (Δ9) and cryptic sequential exons 8 and 9-skipping (Δ8-9) products, as well as a no exon-skipping product. CONCLUSIONS We identified a novel KCNQ splicing mutation 1251+1G>A in forme fruste LQT1, which induces cryptic splicing. Two of the five individuals with mutation experienced VTAs in the setting of hypokalemia, emphasizing the need to increase awareness of the significance of hypokalemia in this subgroup of LQT1 patients.

Parasympathetic dysfunction and antiarrhythmic effect of vagal nerve stimulation following myocardial infarction

Myocardial infarction causes sympathetic activation and parasympathetic dysfunction, which increase risk of sudden death due to ventricular arrhythmias. Mechanisms underlying parasympathetic dysfunction are unclear. The aim of this study was to delineate consequences of myocardial infarction on parasympathetic myocardial neurotransmitter levels and the function of parasympathetic cardiac ganglia neurons, and to assess electrophysiological effects of vagal nerve stimulation on ventricular arrhythmias in a chronic porcine infarct model. While norepinephrine levels decreased, cardiac acetylcholine levels remained preserved in border zones and viable myocardium of infarcted hearts. In vivo neuronal recordings demonstrated abnormalities in firing frequency of parasympathetic neurons of infarcted animals. Neurons that were activated by parasympathetic stimulation had low basal firing frequency, while neurons that were suppressed by left vagal nerve stimulation had abnormally high basal activity. Myocardial infarction increased sympathetic inputs to parasympathetic convergent neurons. However, the underlying parasympathetic cardiac neuronal network remained intact. Augmenting parasympathetic drive with vagal nerve stimulation reduced ventricular arrhythmia inducibility by decreasing ventricular excitability and heterogeneity of repolarization of infarct border zones, an area with known proarrhythmic potential. Preserved acetylcholine levels and intact parasympathetic neuronal pathways can explain the electrical stabilization of infarct border zones with vagal nerve stimulation, providing insight into its antiarrhythmic benefit.

Electroanatomically estimated length of slow pathway in atrioventricular nodal reentrant tachycardia

The length of the slow pathway (SP-L) in atrioventricular (AV) nodal reentrant tachycardia (NRT) has never been measured clinically. We studied the relationship among (a) SP-L, i.e., the distance between the most proximal His bundle (H) recording and the most posterior site of radiofrequency (RF) delivery associated with a junctional rhythm, (b) the length of Koch’s triangle (Koch-L), (c) the conduction time over the slow pathway (SP-T), measured by the AH interval during AVNRT at baseline, and (d) the distance between H and the site of successful ablation (SucABL-L) in 26 women and 20 men (mean age 64.6 ± 11.6 years), using a stepwise approach and an electroanatomic mapping system (EAMS). SP-L (15.0 ± 5.8 mm) was correlated with Koch-L (18.6 ± 5.6 mm; R2 = 0.1665, P < 0.005), SP-T (415 ± 100 ms; R2 = 0.3425, P = 0.036), and SucABL-L (11.6 ± 4.7 mm; R2 = 0.5243, P < 0.0001). The site of successful ablation was located within 10 mm of the posterior end of the SP in 38 patients (82.6 %). EAMS-guided RF ablation, using a stepwise approach, revealed individual variations in SP-L related to the size of Koch’s triangle and AH interval during AVNRT. Since the site of successful ablation was also correlated with SP-L and was usually located near the posterior end of the SP, ablating anteriorly, away from the posterior end, is not a prerequisite for the success of ablation procedures.

V‐A‐A‐V Activation Sequence at the Onset of a Long RP Tachycardia: What is the Mechanism?

A 52-year-old woman with a history of multiple episodes of paroxysmal supraventricular tachycardia underwent electrophysiologic studies and a catheter ablation procedure. The 12-lead electrocardiogram during tachycardia showed a long RP tachycardia with negative P waves in leads II, III, and aVF. At baseline, dual atrioventricular (AV) and ventriculoatrial (VA) nodal conduction was elicited by atrial and ventricular premature stimulation. During intravenous administration of isoproterenol, the earliest site of atrial activation during ventricular pacing was observed near the His bundle, and a previously recorded narrow QRS tachycardia was reproducibly induced by premature or rapid ventricular apical pacing, with an initial V-A-A-V activation sequence (Fig. 1). During tachycardia, the HA and AH intervals measured 71 and 342 milliseconds, respectively, and the earliest atrial activation was recorded at the ostium of the coronary sinus (CS). The earliest first “A” of the initial “V-A-A-V” activation sequence was recorded in the His bundle region, reflecting conduction over a fast pathway (FP), as was observed during ventricular pacing, while the second “A” was recorded near the CS ostium, as was observed during the tachycardia. The interval between the first and second “A” was often shorter than the subsequent tachycardia cycle length. Premature ventricular stimuli delivered during tachycardia while the His bundle was refractory did not reset the atrial cycle. From these observations, what is the mechanism of tachycardia?

Putative Mechanism of a Postpacing Interval Paradoxically Shorter Than the Tachycardia Cycle Length

A 79-year-old man without structural heart disease underwent electrophysiological studies and radiofrequency catheter ablation of drug-refractory paroxysmal atrial flutter (AFl). The 12-lead electrocardiogram showed negative flutter waves in leads II, III, aVF, and V5 and V6, and positive flutter waves in lead V1 and V2, consistent with typical counterclockwise AFl. A 7F InquiryTM eicosapolar electrode catheter (St. Jude Medical, AF Division, Minnetonka, MN, USA) with 2-mm interelectrode spacing was advanced into the coronary sinus (CS) from the right subclavian vein, with its middle electrodes (9–10) placed at the ostium and proximal electrodes (20–11) along the Eustachian ridge (ER). Counterclockwise AFl was confirmed by entrainment pacing at multiple sites along the tricuspid annulus. Double potentials were recorded along the ER during ongoing AFl, with the first potential (DP1) in a proximal-to-distal and the second (DP2) in a distal-to-proximal direction, with fusion of the 2 potentials at the CS ostium (Fig. 1A). Two different postpacing intervals were reproducibly observed after the cessation of entrainment pacing near the ER (Figs. 1B and C). In Figure 1B, the interval between the last pacing stimulus (S) and the first atrial electrogram is equal to, whereas in Figure 1C, the interval is shorter than, the tachycardia cycle length (TCL). What are the (a) mechanism and (b) implications of this observation?

Right Bundle Branch Block Morphology of Ventricular Tachycardia in Arrhythmogenic Right Ventricular Cardiomyopathy

J Cardiovasc Electrophysiol, Vol. 21, pp. 712-713, June 2010.No disclosures.Address for correspondence: Yoshiaki Kaneko, M.D., Ph.D., Department ofMedicine and Biological Science, Gunma University Graduate School ofMedicine, 3-39-22 Showa, Maebashi, Gunma 371-8511, Japan. Fax: +81-27-220-8158; E-mail: kanekoy@showa.gunma-u.ac.jpdoi: 10.1111/j.1540-8167.2009.01692.x

A Case of Type 2 Amiodarone-Induced Thyrotoxicosis That Underwent Total Thyroidectomy under High-Dose Steroid Administration

Amiodarone is used commonly and effectively in the treatment of arrhythmia; however, it may cause thyrotoxicosis categorized into two types: iodine-induced hyperthyroidism (type 1 amiodarone-induced thyrotoxicosis (AIT)) and destructive thyroiditis (type 2 AIT). We experienced a case of type 2 AIT, in which high-dose steroid was administered intravenously, and we finally decided to perform total thyroidectomy, resulting in a complete cure of the AIT. Even though steroid had been administered to the patient (maximum 80 mg of prednisolone), the operation was performed safely and no acute adrenal crisis as steroid withdrawal syndrome was found after the operation. Few cases of type 2 AIT that underwent total thyroidectomy with high-dose steroid administration have been reported. The current case suggests that total thyroidectomy should be taken into consideration for patients with AIT who cannot be controlled by medical treatment and even in those under high-dose steroid administration.